Chronic Lymphocytic Leukemia (CLL) MedDRA version: 21.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Venclyxto® 10 mg film-coated tablets
Product Name: Venclexta®, Venclyxto® or GDC-0199
Product Code: RO5537382
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: VENETOCLAX
CAS Nu
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Ability to comply with the study protocol, in the investigator's judgment - Aged 18 years or older - Have previously untreated documented CLL according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria - CLL requiring treatment according to the iwCLL criteria - Cumulative illness rating scale score =70 mL/min - Hematology values within the following limits, unless cytopenia is caused by the underlying disease (i.e., no evidence of additional BM dysfunction; e.g., myelodysplastic syndrome, hypoplastic BM): o Absolute neutrophil count >=1.0 × 10^9/L, unless there is BM involvement o Platelet count >=75 × 10^9/L and more than 7 days since last transfusion, or >=30 × 10^9/L if there is BM involvement - Adequate liver function as indicated by a total bilirubin, aspartate aminotransferase, and Alanine transaminase 6 months - For women of childbearing potential: agreement to remain abstinent or use contraception and agreement to refrain from donating eggs, women must remain abstinent or use contraceptive methods with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 66
Exclusion criteria
Exclusion criteria: - Transformation of CLL to aggressive non-Hodgkin’s lymphoma - Patients with small lymphocyclic lymphoma - Known central nervous system involvement - Patients with a history of confirmed progressive multifocal leukoencephalopathy - Detected del (17p) or TP53 mutation - An individual organ/system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system - Patients with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia - History of prior malignancy - Patients with infections requiring IV treatment (Grade 3 or 4) within the last 8 weeks prior to enrollment - Evidence of other clinically significant uncontrolled condition(s) including but not limited to active or uncontrolled systemic infection - History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products - Hypersensitivity to fludarabine, bendamustine, cycolphosphamide, rituximab, obinutuzumab, or venetoclax or to any of the excipients - Pregnant women and nursing mothers - Vaccination with a live vaccine <=28 days prior to randomization - Prisoners or patients who are institutionalized by regulatory or court order or persons who are in dependence to the Sponsor or an investigator - History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator’s judgment - Positive test results for chronic hepatitis B virus infection and for hepatitis C - Patients with known infection with HIV or Human T-Cell Leukemia Virus 1 - Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study - Received any of the following agents within 28 days prior to the first dose of study treatment: o Immunotherapy o Radiotherapy o Hormone therapy o Any therapies intended for the treatment of lymphoma/leukemia whether approved or experimental - Patients who have received the following agents: o Strong and moderate CYP3A inhibitors and inducers within 7 days prior to the initiation of study treatment o Steroid therapy for anti-neoplastic intent with the exception of inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids within 7 days prior to the first dose of study drug administration o Consumed grapefruit, grapefruit products, Seville oranges , or star fruit within 3 days prior to the first dose of study drug and throughout venetoclax administration - Inability to swallow a large number of tablets
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the efficacy of venetoclax (Venclexa® or Venclyxto®) in combination with obinutuzumab (Gazyva® or Gazyvaro®) (VEN + G) compared with fludarabine, cyclophosphamide, and rituximab (FCR)/ bendamustine and rituximab (BR) on the basis of minimal residual disease (MRD) response rate;Secondary Objective: - To evaluate the efficacy of VEN + G compared with FCR/BR on the basis of progression-free survival, MRD response rate in PB and BM, objective response rate, complete response rate, duration of objective response, best response achieved, event-free survival, overall survival - To evaluate safety of VEN + G compared with FCR/BR on the basis of nature, frequency, and severity of adverse events, changes in vital signs, physical findings, clinical laboratory test results, premature withdrawals - To compare disease and treatment-related symptoms and to evaluate changes in physical functioning, role functioning, and global health status/quality of life following treatment with the combination of VEN + G compared with FCR/BR in patients with previously untreated CLL without del(17p) or TP53 mutation measured by M.D. Anderson Symptom Inventory (MDASI-CLL) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30);Primary end point(s): 1. MRD response rate measured in PB at Month 15 in the first 140 patients recruited 2. Nature , frequency, and severity of adverse events and serious adverse events;Timepoint(s) of evaluation of this end point: 1. At Month 15 for each patient, Month 36 in the study 2. Up to 28 days after the last dose of study drug, or until initiation of another anti-cancer therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. Every year after disease progression until end of study (up to 46 months) 2-3. At end of treatment response visit (up to 36 months) 4-6. At Month 15 for each patient, Month 36 in the study 7. At end of treatment response visit (up to 36 months) 8. At Month 15 for each patient, Month 36 in the study 9-11. Every year after disease progression until end of study (up to 46 months) 12. Up to 28 days after the last dose of study drug, or until initiation of another anti-cancer therapy 13. Up to 46 months 14-15. Arm A: Day 1 of Cycle 1-12, Day 28 after treatment completion/early termination (TC/ET), follow up (FU) visits; Arm B: Day 1 of Cycle 1-6, Day 28 after TC/ET, end of combination treatment response visit and FU visit;Secondary end point(s): 1. Progression-free survival 2. MRD response rate, in PB at end of treatment response visit 3. MRD response rate in BM at end of treatment response visit 4. Objective response rate 5. Complete response rate 6. MRD response rate in PB in patients with a complete remission /complete remission with incomplete blood count recovery (CR/Cri) at Month 15 7. MRD response rate in BM in patients with a CR/CRi at end of treatment visit 8. Best response 9. Duration of objective response 10. Event-free survival 11. Overall survival 12. Changes in vital signs, physical findings, and clinical laboratory test results during and following study treatment 13. Premature withdrawals 14. Change in disease and treatment-related symptoms following treatment with the combination of VEN + G compared with FCR/BR in patients with previously untreated CLL without del (17p) or TP53 mutation as measured by MDASI-CLL 15. Change in physical functioning, role functioning and health-related quality of life following treatment with the combination of VEN + G compared with FCR/BR in patients with previously with previously untreated CLL without del(17p) or TP53 mutation as measured by EORTC QLQ-C30 | — |
Countries
Australia, France, Italy, Spain, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed